阅读说明：本技术 丹参酮iia磺酸钠在制备伴随血液中同型半胱氨酸升高的急性或慢性疾病的药物中的应用 (Application of tanshinone IIA sodium sulfonate in preparation of medicine for treating acute or chronic diseases accompanied with increase of homocysteine in blood ) 是由 唐靖一 陈昕琳 周忠焱 马子霖 赵外荣 肖颖 施雯婷 于 2018-09-13 设计创作，主要内容包括：本发明涉及丹参酮IIA磺酸钠单独或者作为有效成分在制备伴随血液中同型半胱氨酸升高的急性或慢性疾病的药物中的应用。本发明运用血管内皮细胞、心肌细胞、神经细胞、离体血管模型,模拟高同型半胱氨酸对心脑血管系统的损伤作用,发现丹参酮IIA磺酸钠对高同型半胱氨酸引起的心脑血管损伤具有保护和/或治疗作用,弥补了对抗同型半胱氨酸引起的心脑血管损害的保护和/或治疗药物的空白。本发明提供的药物适用于引起血液内同型半胱氨酸异常升高的疾病,只需要在血液内达到有效浓度即可发挥对抗同型半胱氨酸引起心脑血管损伤的保护和/或治疗作用,为血液中同型半胱氨酸升高疾病的心脑血管损伤治疗提供了更好的选择。(The invention relates to application of tanshinone IIA sodium sulfonate in preparation of drugs for treating acute or chronic diseases accompanied with increase of homocysteine in blood independently or as an effective component. The invention uses vascular endothelial cells, myocardial cells, nerve cells and isolated blood vessel models to simulate the damage effect of homocysteine on the cardiovascular and cerebrovascular systems, finds that the tanshinone IIA sodium sulfonate has the protection and/or treatment effect on the cardiovascular and cerebrovascular damage caused by homocysteine, and fills the blank of protection and/or treatment medicines for resisting the cardiovascular and cerebrovascular damage caused by homocysteine. The medicine provided by the invention is suitable for diseases causing abnormal increase of homocysteine in blood, can play a role in protecting and/or treating cardiovascular and cerebrovascular injuries caused by resisting homocysteine only by reaching effective concentration in blood, and provides a better choice for treating cardiovascular and cerebrovascular injuries caused by diseases causing the increase of homocysteine in the blood.)

1. Application of tanshinone IIA sodium sulfonate in preparing medicine for treating acute or chronic diseases accompanied with increase of homocysteine in blood independently or as effective component is provided.

2. Use according to claim 1, wherein the acute and/or chronic disease accompanied by an increase in homocysteine in the blood is hypertension, coronary heart disease, heart failure, arrhythmia, atherosclerosis or stroke.

3. The use according to claim 1, wherein the acute and/or chronic disease accompanied by an increase in homocysteine in the blood is cognitive disorders, senile dementia or migraine.

4. The use according to claim 1, wherein the acute and/or chronic disease associated with elevated homocysteine in the blood is acute or chronic renal failure.

5. The use according to claim 1, wherein the acute and/or chronic disease accompanied by an increase in homocysteine in the blood is diabetes, gout or osteoporosis.

6. The use according to claim 1, wherein the acute and/or chronic disease accompanied by an increase in homocysteine in the blood is schizophrenia.

7. The use according to claim 1, wherein the acute and/or chronic disease associated with elevated homocysteine in the blood is cataract or glaucoma.

8. The use according to claim 1, wherein the acute and/or chronic disease accompanied by an increase in homocysteine in the blood is cancer or a congenital disease.

9. The use according to claim 1, wherein the acute and/or chronic disease associated with elevated homocysteine in blood is drug-induced elevated homocysteine in blood.

10. The use as claimed in claim 1, wherein the tanshinone IIA sodium sulfonate is in the form of an injection, tablet, capsule, liposome, granule, oral liquid or pill using tanshinone IIA sodium sulfonate as raw material or sodium tanshinone IIA sulfonate as component.

Technical Field

The invention belongs to the field of pharmacy, and relates to application of tanshinone IIA sodium sulfonate in preparation of medicines for preventing and/or treating cardiovascular and cerebrovascular injury related diseases caused by hyperhomocysteine

Background

Homocysteine is an independent risk factor of cardiovascular and cerebrovascular diseases such as coronary heart disease, atherosclerosis and the like, and the pathogenesis of homocysteine comprises the influence on the function of vascular endothelium, the promotion of smooth muscle proliferation, the promotion of thrombosis, cardiovascular toxicity and the like. Some nephropathy, liver disease, metabolic disease, nervous system disease, cancer, some medicine intake and other clinical manifestations are abnormal elevation of homocysteine in blood. At present, the medicines for clinically preventing and treating the homocysteine are mainly compound preparations containing B vitamins and folic acid for interfering in a methyl transferring way or a sulfur transferring way of the homocysteine or simultaneously interfering in the two ways, but the improvement effect of the medicines on the incidence rate and the death rate of cardiovascular and cerebrovascular diseases such as atherosclerosis and the like is supported by lack of authoritative evidence. Therefore, the development of a protective agent for resisting the cardiovascular damage caused by the hyperhomocysteine has important significance for treating related diseases, and has wide application prospect.

The tanshinone IIA sodium sulfonate is a water-soluble derivative of tanshinone IIA in traditional Chinese medicine salvia miltiorrhiza bunge, greatly enhances water solubility by introducing sodium sulfonate groups, is clinically prepared into an injection, overcomes the problems of poor water solubility, low oral bioavailability and difficulty in drug formation of the tanshinone IIA, and has the CAS No. as follows: 696659-80-9, the structural formula is:

the tanshinone IIA sodium sulfonate injection is widely applied to treatment of diseases such as clinical coronary heart disease, angina pectoris, ventricular premature beat and the like, modern pharmacology shows that the tanshinone IIA sodium sulfonate injection has pharmacological activities such as oxidation resistance, inflammation resistance and the like, and has a definite cardiovascular protection effect, but the tanshinone IIA sodium sulfonate injection has no report on resisting cardiovascular damage caused by hyperhomocysteine.

Disclosure of Invention

In view of the above-mentioned deficiencies of the prior art, according to the embodiments of the present invention, it is desirable to provide an application of tanshinone IIA sodium sulfonate in preparing a medicine for treating and preventing cardiovascular and cerebrovascular injury related diseases accompanied by cysteine increase.

In order to complete the invention, the inventor adopts a plurality of models to simulate the cardiovascular and cerebrovascular injury effect of the homocysteine, and researches the efficacy of the tanshinone IIA sodium sulfonate for treating and preventing the cardiovascular and cerebrovascular injury caused by the homocysteine.

In the invention, the tanshinone IIA sodium sulfonate is used alone or as an effective component in preparing the medicine for treating acute or chronic diseases accompanied with the increase of homocysteine in blood.

According to the embodiment of the present invention, the aforementioned acute and/or chronic diseases accompanied with elevated homocysteine in blood include, but are not limited to, (1) cardiovascular and cerebrovascular diseases such as hypertension, coronary heart disease, heart failure, arrhythmia, atherosclerosis, stroke, etc., (2) nervous system diseases such as cognitive disorder, senile dementia, migraine, etc., (3) renal system diseases such as acute and chronic renal failure, etc., (4) metabolic diseases such as diabetes, gout, osteoporosis, etc., (5) mental diseases such as schizophrenia, etc., (6) eye diseases such as cataract, glaucoma, etc., (7) cancer (8) congenital diseases (9) elevated homocysteine in blood caused by drugs, etc.

According to an embodiment of the present invention, the dosage form of the tanshinone IIA sodium sulfonate of the present invention is a compound preparation using tanshinone IIA sodium sulfonate as a raw material preparation or using tanshinone IIA sodium sulfonate as a component, and includes, but is not limited to, an injection, a tablet, a capsule, a liposome, a granule, an oral liquid, a pill, and the like.

The homocysteine obviously causes the toxicity of vascular endothelial cells and myocardial cells, the migration inhibition of the endothelial cells and the dysfunction of vasoconstriction and relaxation, and shows that the homocysteine has obvious toxicity to the cardiovascular system. Research data of the invention show that tanshinone IIA sodium sulfonate can effectively inhibit cardiovascular damage caused by homocysteine, and can play a role in preventing and treating cardiovascular damage for various diseases which show that homocysteine in blood is increased. In addition, the tanshinone IIA sodium sulfonate is a clinically used patent medicine, and has a huge market application prospect for expanding the clinical indications.

Drawings

Figure 1 toxic effect of homocysteine (Hcy) on endothelial cells (P <0.001 compared to control).

Figure 2 tanshinone IIA sodium sulfonate (STS) caused a protective effect on homocysteine (Hcy) toxicity of vascular endothelial cells (# P <0.001 compared to control, P <0.01 compared to model, P < 0.001).

FIG. 3 shows the protective effect of tanshinone IIA sodium sulfonate (STS) on homocysteine (Hcy) induced inhibition of vascular endothelial cell migration (P # 0.001, # P <0.05 compared to control group; P # 0.05, P # 0.01 compared to model group).

Figure 4 toxic effect of homocysteine (Hcy) on cardiomyocytes (P <0.05, P <0.001 compared to control group).

Figure 5 protective effect of tanshinone IIA sodium sulfonate (STS) on homocysteine (Hcy) induced toxicity of cardiomyocytes (# P <0.001 compared to control, P <0.01 compared to model, P < 0.001).

Figure 6 effect of homocysteine (Hcy) on the impaired thoracic aortic systolic function in rats (P <0.001 compared to control).

FIG. 7 shows the protective effect of tanshinone IIA sodium sulfonate (STS) on homocysteine (Hcy) on the systolic function impairment of rat thoracic aorta (ratio # # # P <0.001 to control group, and ratio # # P <0.001 to model group).

Figure 8 toxic effect of homocysteine (Hcy) on nerve cells (P <0.001 compared to control).

Figure 9 protective effect of tanshinone IIA sodium sulfonate (STS) on homocysteine (Hcy) induced toxicity of nerve cells (# P <0.001 compared to control, P <0.01 compared to model, P < 0.001).

Detailed Description

The invention is further illustrated with reference to the following figures and specific examples. These examples are to be construed as merely illustrative and not limitative of the remainder of the disclosure in any way whatsoever. After reading the description of the invention, one skilled in the art can make various changes and modifications to the invention, and such equivalent changes and modifications also fall into the scope of the invention defined by the claims.